Psoriasis regression analysis of MHC loci identifies shared genetic variants with vitiligo

Abstract

Psoriasis is a common inflammatory skin disease with genetic components of both immune system and the epidermis. PSOR1 locus (6q21) has been strongly associated with psoriasis; however, it is difficult to identify additional independent association due to strong linkage disequilibrium in the MHC region. We performed stepwise regression analyses of more than 3,000 SNPs in the MHC region genotyped using Human 610-Quad (Illumina) in 1,139 cases with psoriasis and 1,132 controls of Han Chinese population to search for additional independent association. With four regression models obtained, two SNPs rs9468925 in HLA-C/HLA-B and rs2858881 in HLA-DQA2 were repeatedly selected in all models, suggesting that multiple loci outside PSOR1 locus were associated with psoriasis. More importantly we find that rs9468925 in HLA-C/HLA-B is associated with both psoriasis and vitiligo, providing first important evidence that two major skin diseases share a common genetic locus in the MHC, and a basis for elucidating the molecular mechanism of skin disorders.

Figure 1. Recombination rates and p values from single SNP associations at four starting SNPs and rs9468925 in HLA-C/HLA-B appeared in four models, based on combined Japanese and Han Chinese sample in HapHap data(JPT+CHB) and is not in LD with all of four starting SNPs.

Figure 2. Venn diagram of SNPs selected in four models.

Intersection indicates shared SNPs selected from different models.